Our investigations will emphasize the ways in which the molecular mechanisms that control the operons of the ilv regulon in Escherichia coli respond to physiological signals and how these operons coordinate their regulation. For example, we will study how the ilvBN and ilvGMEDA operons respond to carbon shifts during growth and what roles the attenuators play in these responses. We will also address a major question regarding attenuation which has not yet been seriously considered; that is, what is the importance of codon context in the leader polypeptides of attenuators. In this regard we have advanced an intriguing hypothesis for codon pair usage that may have broad implications for atenuation and protein synthesis. We further propose to determine the molecular mechanisms responsible for the regulation of the ilvYC gene and the valyl-tRNA synthetase gene, and the roles of the AHAS isozymes in the regulation of isoleucine-valine biosynthesis.